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Aldehyde oxidase 1 gene is regulated by Nrf2 pathway
Kenichiro Maeda1, Takashi Ohno, Shizuka Igarashi
1Division of Radiological Technology, Department of Health Sciences, School of Medicine, Hokkaido University, Kita-12, Nishi-5, Sapporo 060-0812, Japan.
Gene
|June 19, 2012
Summary
The Nrf2 pathway regulates aldehyde oxidase-1 (AOX1) gene expression. Nrf2 binds to antioxidant responsive elements (ARE) in the AOX1 gene
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Aldehyde oxidase (AOX) is a molybd-flavo enzyme family member catalyzing hydroxylation and oxidation reactions.
- Aldehyde oxidase-1 (AOX1) is liver-expressed, oxidizing aldehydes and nitrogenous heterocycles, including drugs.
Purpose of the Study:
- To identify physiological substrates of AOX1.
- To elucidate the regulatory mechanisms governing AOX1 gene expression.
Main Methods:
- Reporter transfection assays
- Electrophoretic mobility shift assay (EMSA)
- Chromatin immunoprecipitation (ChIP) analysis
Main Results:
- The Nrf2 pathway was identified as a key regulator of AOX1 gene expression.
- Two antioxidant responsive elements (ARE) were found in the 5' upstream region of the rat AOX1 gene.
- Nrf2 was demonstrated to bind to and strongly activate the rat AOX1 gene.
Conclusions:
- The Nrf2 pathway plays a crucial role in regulating AOX1 gene expression.
- Understanding AOX1 regulation by Nrf2 provides insights into xenobiotic metabolism and drug interactions.
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